JPH0466524A - Composition for use in oral cavity - Google Patents

Abstract

PURPOSE:To provide the title composition having high inhibitory activity to collagenase, effective for the prevention and therapy of periodontosis, also extremely high in the safety in its use, containing gallotannin. CONSTITUTION:The objective composition can be obtained by formulating (A) normally 0.001 - 2.0 (pref. 0.01 - 1.0)wt.% of gallotannin present in various crude drugs such as Japanese gall, gall, paeonia albiflora and paeonia suffruticosa skin and widely distributed over the plant kingdom including oak trees, wax trees and myrobalan, and finding applications such as deproteinizing agents, stegnotics and leather in (B) a food such as chewing gum, candy or beverage, or a composition for use in the oral cavity such as toothpaste, mouth- wash, troches or liniment. The present composition has high inhibitory activity to collagenase causing the collagen absorption at the gingiva and alveolar bone in periodontosis, therefore, being effective for the prevention and therapy of periodontosis, and also being extremely high in the safety in its use regardless of the amount of the gallotannin formulated.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention provides an oral composition containing gallotannin, more specifically, a composition containing gallotannin and having human-derived collagenase inhibitory activity. The present invention relates to an oral composition useful for preventing and treating periodontal disease.

[Conventional technology]

Periodontal disease is a general term for inflammatory diseases that include various pathologies in the periodontal tissue, but generally there are two main types: gingivitis, where inflammation is limited to the gingival region, and periodontitis, where inflammation reaches the alveolar bone and becomes chronic. Separated. Periodontitis used to be called alveolar pyorrhea, but as it becomes chronic, it causes destruction of the gingiva and alveolar bone, leading to tooth loss. Periodontal disease accounts for 50% of tooth loss, and approximately 80% of middle-aged and elderly people are affected.

Periodontal disease is caused by a specific group of bacteria in the plaque in periodontal pockets, especially the black pigment-producing Hatteroides (
Bacteroides) pathogenic theory is considered to be the most likely (for example, Journal of C11nical
Periodontology, vol. 13, p. 912, 1986). Its circumferential Mi weave destruction action is as follows:
It is thought that direct acting factors derived from bacteria (such as enzymes and endotoxins) and indirect acting factors (mediated by the host's immune response) are involved, but either way, the result is that collagen in the gingiva and alveolar bone is damaged. What they have in common is that they are decomposed and collected (American Journal of Pa.
thology, Vol. 92, p. 509, 1978).

Collagenase-derived enzymes (collagenases) associated with periodontal disease are attracting attention, including those derived from Batteroides and those derived from gingival fibroblasts. The former has recently been partially purified and is a rare enzyme that requires metals and thiols at the same time, but there are still many unknowns (Journal of Pedia
Riodontal Research, Volume 23,
258, 1988). On the other hand, fibroblast-derived interstitial collagenase (hereinafter referred to as collagenase unless otherwise specified) has been elucidated in detail and its primary structure has been clarified (The Journal of Biologic
alChemistry, Volume 261, Page 6600, 19
Collagenase is a rate-limiting enzyme in degrading interstitial collagen (type I, type ■, and type ■ collagen) in connective tissue, and plays an important role in collagen metabolism. Collagenase activity increases in inflamed gingiva (Journal of Per
iodontal Research, vol. 16, 41
7, 1981), and that collagen is reduced from the early stages of gingivitis (^rchieves).
of Oral Biology, Volume 18, 89
9, 1973), it is thought that gingival collagenase is deeply involved in the progression of periodontal disease.

Conventionally, removal of plaque and tartar in periodontal pockets by scaling or root planing, removal of periodontal pockets (gingivectomy), etc. have been used to prevent and treat periodontal disease. Additionally, a therapeutic agent containing the antibacterial agent minocycline has recently been developed as a drug therapy. For minocycline,
It has been reported that it has not only antibacterial activity but also the activity of inhibiting collagenase derived from Hatatheroides and neutrophils in vitro (Journal of the Jap
anese As5ocation of Peri
odontology, vol. 30, p. 182, 1988
(see year).

[Problem to be solved by the invention]

The above-mentioned known methods are based on physical, surgical, or drug treatment as directed by a physician. However, considering that periodontal disease is a common disease with a high prevalence, and that the condition tends to worsen before treatment by a doctor, it is important to avoid using foods such as gum, candy, drinks, and toothpaste. It is desirable to use food-derived materials with high safety in oral materials such as mouthwashes that eliminate the aforementioned pathogenic factors and are useful for the prevention and treatment of periodontal disease.

An object of the present invention is to provide a highly safe food material that is effective in preventing and improving periodontal disease.

[Means for solving cyAtu] Among the above-mentioned causes of periodontal disease, the present inventors have discovered that inhibiting the activity of collagenase, which plays an important role in controlling the decomposition and absorption of gingival and alveolar bone collagen, is a periodontal disease. Focusing on its effectiveness in preventing and improving disease, we conducted extensive research to find collagenase inhibitors from a wide variety of food-derived materials, and found that gallotannin, a component of goblets and gallic berries, has strong collagenase inhibitory activity. This discovery led to the completion of the present invention.

The present invention relates to an oral composition characterized by containing gallotannin.

Gallotannin is a gallogoglucose that is widely distributed in the plant world, including five-fold gall, gall, various herbal medicines such as Xun medicine and oyster peel, and kaji, snail, and myrobalan. It is a combination of gallic acid. In the case of five-fold tannin, an average of 8.3 molecules of gallic acid are bound to one molecule of glucose, and the average molecular weight is 1434. It is known for its uses as a protein remover, an anti-astringent agent, and a red skin.

The method for producing gallotannin used in the present invention is not particularly limited, and any commonly used method may be used. For example, from China Five (@r and Turkey Five Times), leaching is carried out using the water leaching method, alcohol leaching method, or alcohol/ether leaching method, and after purification by removing pigments, resins, etc., it is reduced to a coarse powder by vacuum condensation. Usually, about 50 to 60% from Chinese Gobako, and about 70% from Turkey Gobako.
obtained with a yield of .

When gallotannin obtained by such a method is used in the oral composition of the present invention, commonly used known components can be optionally added depending on the type of the composition.

Such oral compositions may be in the form of sterilizers, solid preparations, or semi-isomorphic preparations, and preferred compositions include foods such as chewing gum, candy, and drinks, or dentifrices, mouthwashes, and troches. Agents, liniment liquids, etc.

The excipients or auxiliary agents used to produce these oral compositions are not particularly limited, and may be appropriately selected from those commonly used for the same purpose depending on the dosage form. For example, lactose, magnesium stearate, sorbift, and mannitol.

Carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose Sankarin, sodium lauryl sulfate sodium lauroyl sarcosinate, glycerin polyethylene glycol, polyvinyl alcohol, laginan, gum arabic, ethanol, menthol, fatty acids, citric acid, dibasic calcium silicate phosphate, hydroxyapatite , calcium carbonate, titanium dioxide, etc. are used. However, the golden rule,
Care must be taken when used in combination with metal salts, glue, TJ powder, etc. as poorly soluble compounds may be formed.

In the above composition, a sweetener coloring agent commonly used in foods,
Flavoring agents, preservatives, etc. can be used as appropriate, and bactericidal agents such as chlorhexidine and antibiotics such as ampicillin can be added to enhance the effect of preventing and improving periodontal disease.

The amount of gallotannin in the oral composition useful for the prevention and treatment of periodontal disease produced in this way varies depending on the dosage form, but is usually 0.001 to 2.0% by weight, preferably 0.01% by weight. It is desirable that the amount is 1.0% by weight.

〔Effect of the invention〕

The oral composition according to the present invention contains gallotannin, so it has excellent inhibitory activity against collagenase, which is the cause of collagen absorption in the gingiva and alveolar bone in periodontal disease, and is useful for the prevention and treatment of periodontal disease. It is useful and has extremely high safety in use, regardless of the amount blended.

[Test Example] Human collagenase inhibitory effect of gallotannin 1. Test gallotannin tannic acid AL (Fuji Chemical) 2. Collagenase Collagenase is purified by the method described in Japanese Patent Application No. 1-238941.

3. Measurement of collagenase inhibitory activity To measure the inhibitory activity of test gallotannin against collagenase, test gallotannin was added to measurement buffer (0.2M salt, 5mM calcium chloride, 0.05% by volume Br1j-3).
5 and 5 containing 0.02% sodium azide by volume.
A solution dissolved in 0mM) Lis-HCl buffer, pH 7.5) and a known amount of collagenase solution were mixed, and type I collagen labeled with fluorenosein isothiosoanate (manufactured by Cosmohio) was used as a substrate. Nagai et al.'s method (J
apaneseJournal of Inflama
tion, Vol. 4, p. 123, 1984) by measuring collagenase activity.

4. Test results are shown in Table 4. The test gallotannin had a dose-dependent collagenase inhibitory activity, and the IC5゜Table 83.3 62.5 40.0 73.6 56.6 19.9 The following is a method for producing an oral composition containing gallotannin. Here are some examples.

[Example-1] Chewing gum composition Weight % Chewing gum hese Powder sugar Glucose starch syrup (15% water) Gallotannin flavoring 20.0 50.9 18.0 1.0 Total amount of chewing gum hese kept at 40°C and total amount of Add the starch syrup to the Neegu and mix for 10 minutes, then add 1/2 of the powdered sugar.
173 amounts of powdered sugar was added and kneaded for 5 minutes. Next, the gallotannin was mixed with the remaining 173 amounts of powdered sugar, then added and kneaded for 5 minutes to form a gum [Example-2] Nougat composition ■ Egg white powder water ■ Granulated sugar starch syrup (water content 30%) Parts by weight of water ■ Milk powder, vegetable oil, fat, flavor, coloring agent 0.4 0, 3 ■ Gallotannin 0, 2 ■ Mix and whisk. ■Cold temperature up to 130℃. Add ■ little by little to ■ and whisk further. To this, 2 was added and cooled to 90° C. while mixing. After 2 was added and mixed well, it was spread on a cooling plate and molded to obtain a nougat.

[Example-3] Toothpaste composition Weight % Phosphoric acid Power Runum Glycerin Carrageenan Sodium lauryl grate Sankarin Rose wood Butyl xybenzoate Chlorhexidine Di Gluconey Flavor Gallotannin Water 1.2 1.0 0, 0 O5 0.1 0.1 0.3 Remaining amount Manufactured according to conventional methods. That is, after measuring the prescribed amounts of water, glycerol raginan, saccharin, phthyl paraoxybenzoate, chlorhequindine digluconate, fragrance, and gallotannin and mixing them to swell the binder, the second
Calcium phosphate sodium lauryl sulfate is added, and after further mixing and defoaming, the mixture is filled into a tube to obtain a toothpaste.

[Example 4] Toothpaste A toothpaste is obtained in the same manner as in Example 3 except that the amount of gallotannin added is 1.0% by weight.

[Example-5] Lozenge formulation composition Weight % Volutylene Grinifur 6000 Anhydrous silicic acid Stearate Magnum talc Hydroquine Probil Cellulose Gallotannin Mannitol 2, 0 1, 0 0.6 0, 3 0, 7 Remaining amount Manufacture the troche of the above formulation according to the conventional method.

[Example-5] Mouthwash Mixture composition weight% ethanol saccharin sodium fragrance Sucrose fatty acid ester gallotannin water 20.0 0.1 1.0 0.5 0.5 Remaining amount A mouthwash having the above formulation is manufactured according to a conventional method.

Claims (1)

[Claims] Oral composition characterized by containing gallotannin